Differential leukocyte counts of SJL/J mice with dysferlinopathy treated with resveratrol and coenzyme Q10

Abstract

Dysferlinopathies include Limb-Girdle Muscular Dystrophy type 2B and Miyoshi Myopathy, which exhibit an autosomal recessive inheritance pattern of the dysferlin gene and characteristic inflammatory infiltrate in muscle. A study of prospective treatment options was conducted on SJL/J mice, a natural model for dysferlinopathy. The animals are immunocompetent but have elevated levels of circulating T-cells. A baseline termination of SJL/J mice was made at 14 weeks, and differential leukocyte counts determined for these animals through microscopy. After administration of resveratrol and Coenzyme Q10 exclusively and in combination to the four treatment groups for approximately three months, the remaining six groups (negative and positive controls as well as four treatment groups) were terminated and differential leukocyte counts once again determined. Eosinophil counts were significantly higher in the baseline termination group than all other experimental groups assessed except for the negative control SWR/J mice, possessing normal muscle and used in research as a general purpose strain. Eosinophil granules are suggested to reduce inflammation caused by other leukocytes. At onset of dysferlinopathy between four and six weeks of age, the increase in eosinophil counts could very likely be a compensation mechanism to decrease initial inflammation in the muscular tissues of the dysferlinopathic mice. Neutrophil counts of the baseline termination group were significantly higher only when compared to the resveratrol/Coenzyme Q10 combination group. Neutrophils are linked to early inflammatory responses and often sensitised in self-antigen recognition characteristic of autoimmune disease, a known complication in the SJL strain. Thus the higher neutrophil count in the six week old mice is probably related to inflammation at disease onset, but may also be indicative of autoimmunity; whereas the eosinophil counts may possibly play a more definitive role in the pathogenesis of dysferlinopathy. Further morphological studies will serve to clarify the roles of these leukocytes in dysferlinopathy.